The endocrine changes that occur in the ovary of older women are poorly defined. It is known that complete ovarian senescence leads to decreased estrogen and progestin production and to increased androgen production. (Longcope, 1971, 1979). Complete estrogen deficiency is prevented through the aromatization of androgens to estrogens (Frisch et al., 1981; Kwa et al., 1978; Marshall et al., 1977, 1978; Mc Natty et al., 1980). Incomplete ovarian function prior to the menopause leads to the initiation of gonadotropin "escape" (Sherman et al., 1979; van Look et al., 1977; Metcalf, 1979). While the preferential increase of FSH over LH, episodes of inverted gonadotropin ratios (Metcalf et al., 1981b; Rebar et al., 1982; Sherman and Korenman, 1976), and periods of hyperestrinism (Shideler et al., 1989; Santoro et al., 1996) preceding menopause suggest that an inhibin-like substance may be the primary factor leading to gonadotropin escape and irregular ovarian function, definitive studies to establish this relationship have not been conducted as yet. The use of daily urine sampling provides an alternative to repetitive blood sampling for longitudinal studies and reduces subject burden, but ethical considerations relating to endocrine interventions have limited clinical investigation of these processes in older women to observational studies. The proposed studies will investigate the aged macaque monkey as a model for study of the human menopausal transition and test four hypotheses related to the feedback mechanism of pituitary gonadotropin escape. The laboratory macaque has a menstrual cycle and appears to experience ovarian senescence for years prior to somatic senescence. New assay systems have been developed that permit the same endocrine methods for evaluating ovarian functions to be applied to the macaque as have been previously employed in the study of women in the perimenopausal transition. By utilizing the same hormone measurements in macaques and in women, we will develop endocrine data in the macaque model that are directly comparable to those obtained in studies of human subjects.